The Woods Hole Oceanographic Institution (WHOI) has signed a $1.18 million agreement with the Flatley Discovery Lab in Charlestown, Mass., to investigate and supply marine microbial extracts as possible treatments for cystic fibrosis (CF).
The life-shortening respiratory disease has eluded attempts at a cure, although researchers have been successful in some cases at adding years to a person’s lifespan, primarily through treatment with antibiotics.
Now, WHOI is joining Flatley in a novel approach to attacking CF. WHOI microbiologist and chemist Tracy Mincer and his colleagues will provide undersea microbes that Flatley scientists can use in their attempt to stimulate the mutated CFTR (Cystic Fibrosis Trans-membrane Conductance Regulator) gene to work normally.
“The collaboration between my laboratory at WHOI and the Flatley Discovery Lab represents an exciting opportunity to explore the chemical diversity of a vast array of marine microbes and apply this resource to finding therapeutic agents for cystic fibrosis,” Mincer said. “To make host tissues work at normal levels is very exciting. Seeing the science that Flatley is doing has inspired me.”
Cystic fibrosis is caused by a mutation in a particular part of the body’s machinery for sodium transport across a membrane, the CFTR gene, Mincer said. “That causes the mucous layer in the lungs to be thick and prone to infection.” Traditional treatment with antibiotics is limited, he said, because the opportunistic microbial infection biofilm is “hard to kill.”
Flatley Discovery Lab, he says, is on a track that could carry CF treatment far beyond the use of antibiotics.
John Flatley, president and CEO of the Lab, approached WHOI in February “seeking small molecules to correct the underlining cause of CF.” “They came to us with a new way to look for cures for cystic fibrosis,” Mincer said. “Although my research program is focused on fundamental aspects of microbial chemical ecology, the opportunity to apply my work to human betterment is a principal goal of mine that a collaboration with the Flatley Discovery Lab will fulfill.”
“Flatley Discovery Lab feels extremely fortunate to collaborate with a world renowned organization located within our immediate area in our focus to find small molecules that target the root cause of cystic fibrosis,” said Flatley.
The Flatley Discovery Lab was attracted to Mincer’s work with undersea microbes. Mincer co-discovered a chemotherapeutic agent now in clinical trials for the slow-growing cancer multiple myeloma and is compiling a library of phytoplankton, fungi, and other microbes in his WHOI lab to test for more biomedical applications as well as ecologically based functions.
The phytoplankton are related to organisms that have shown immense promise in biomedicine, Mincer said, producing metabolites of unprecedented diversity and structure. Taking advantage of the exploration resources at WHOI, this project also aims to probe the “fringes” of the planet that are extremely difficult to access, such as hydrothermal vent communities, and deep sub-surface samples from WHOI’s deep-sea drilling program.
Mincer’s plan is to provide chemical extracts from diverse marine microbes– particularly marine actinomycetes, which are similar to fungi–whose distant relatives on land have been a proven resource in drug-discovery for the past 50 years. Such substances, he said, “are responsible for 70 percent of antibiotics on the market today.”
He plans a two-pronged approach through generating chemical extracts from cultures that already exist in his collection and the WHOI culture collection, as well as those that will be isolated through investigating new environments, such as offshore waters and tidal flats. “This [grant] will allow my group to explore microbial ‘space’ in an unprecedented fashion,” he said. “We will use ecology and natural history to guide us in choosing the appropriate microbes.”
WHOI is expected to provide 2,000 to 4,000 extracts per year. Mincer and his colleagues will locate, grow, extract and isolate targeted substances so that Flatley scientists can access the rich microbial metabolite diversity for their clinical studies. His approach is based in deciphering “how microbes interact as a fabric in the marine environment…The ocean is a living thing.
“Another particular strength that I envision with this collaboration is the opportunity to work closely with the Flatley Discovery Lab as active chemical extracts are found,” he said. “This will greatly accelerate re-testing and speed the process of pure compound isolation.”
“We are very pleased to embark on this new endeavor with the Flatley Discovery Lab,” said Susan K. Avery, WHOI president and director. “WHOI scientists like Tracy Mincer are developing materials, processes and techniques that may have wide-ranging biotechnological applications.
“Through the characterization and monitoring of biological and chemical processes of ocean microbes, we are able to identify particular molecules that could have great potential in the eventual treatment of many diseases,” Avery added. “Our collaboration with the Flatley Discovery Lab will focus on cystic fibrosis in particular; however, this unique relationship will build the Institution’s capacity to develop additional biomedical collaborations in the future, so we are particularly grateful that Mr. Flatley sought us out.”
Richard Fitzpatrick, COO and CSO of the lab, said, “Coupling WHOI’s unique library of marine micro-organism natural product extracts with FDL’s cystic fibrosis drug discovery pipeline will create a unique opportunity to discover novel therapeutics for CF patients.”
Mincer emphasized his enthusiasm for the partnership. “It’s very important for relationships to exist like this one between WHOI and industry,” he said. “Industry can’t do a lot of things in basic research, things that we can provide. Without compromising our science, we can have a fruitful relationship with industry.”